CHANGES OF NITRIC OXIDE SYNTHASE AND HYDROGEN SULFIDE IN BLOOD LYMPHOCYTES IN THE ACUTE PERIOD OF POLYTRAUMA

2019 ◽  
Vol 72 (8) ◽  
pp. 1473-1476
Author(s):  
Nataliya Matolinets ◽  
Helen Sklyarova ◽  
Eugene Sklyarov ◽  
Andrii Netliukh
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Tissue Injury ◽  
Traumatic Injury ◽  
Cell Types ◽  
No Synthase ◽  
Septic Complications ◽  
Acute Period ◽  
Gaseous Transmitters ◽  
The Moment

Introduction: Polytrauma patients have high risk of shock, septic complications and death during few years of follow-up. In recent years a lot of attention is paid to gaseous transmitters, among which are nitrogen oxide (NO) and hydrogen sulfide (H2S). It is known that the rise of NO and its metabolites levels occurs during the acute period of polytrauma. Nitric oxide and hydrogen sulfide are produced in different cell types, among which are lymphocytes. The aim: To investigate the levels of NO, NOS, iNOS, еNOS, H2S in lymphocytes lysate in patients at the moment of hospitalization and 24 hours after trauma. Materials and methods: We investigated the levels of NO, NO-synthase, inducible NO-synthase, endothelial NO-synthase, H2S in lymphocytes lysate in patients at the moment of hospitalization and 24 hours after trauma. Results: The study included 20 patients with polytrauma who were treated in the intensive care unit (ICU) of the Lviv Emergency Hospital. Tissue injury was associated with an increased production of NO, NOS, iNOS, еNOS during the acute period of polytrauma. At the same time, the level of H2S decreased by the end of the first day of traumatic injury. Conclusions: In acute period of polytrauma, significant increasing of iNOS and eNOS occurs with percentage prevalence of iNOS over eNOS on the background of H2S decreasing.

The role of nitric oxide in iron-induced rat renal injury

2004 ◽  
Vol 23 (11) ◽  
pp. 533-536 ◽  
Author(s):  
M Kadkhodaee ◽  
A Gol
Keyword(s):  
Nitric Oxide ◽  
Renal Function ◽  
Vitamin E ◽  
Renal Injury ◽  
Tissue Injury ◽  
Renal Tissue ◽  
No Synthase ◽  
Plasma Vitamin ◽  
Anti Oxidant ◽  
Plasma Vitamin E

Iron overload and enhanced hydroxyl radical (•OH) formation have been implicated as the causative factors of oxidative stress in different organs. Both pro-oxidant and anti-oxidant properties have been reported for nitric oxide (NO) in iron-mediated tissue injury. To determine the contribution of NO to iron-induced renal injury, eight groups of rats (eight in each group) were studied as follows: control (normal saline), L-Arg (L-arginine as a substrate of NO synthase, 400 mg/kg), L-NAME (an inhibitor of NO synthase, 8 mg/kg), Fe (iron dextran, 600 mg/kg), DFO (deferroxamine as a chelator of iron, 150 mg/kg), Fe+L-Arg, Fe+L-NAME, DFO+L-Arg. Twenty-four hours after the injections, blood samples were taken and kidneys removed for biochemical analysis. Plasma creatinine and urea were used to stimulate renal function. Renal tissue and plasma vitamin E levels, the most important endogenous fat soluble antioxidant, were measured by HPLC and UV detection. In this study, renal function was markedly reduced in the Fe group compared to controls (creatinine, 1.02± 0.05 mg/dL versus 0.78±0.04 P <0.05; urea, 49.59±1.69 mg/dL versus 40.75±0.86, P <0.01). Vitamin E levels were significantly lower in the Fe group compared to controls (plasma P <0.01; renal tissue P <0.05). Administration of L-Arg to Fe-treated groups prevented these reductions. L-NAME increased iron-induced toxicity significantly, demonstrated by further reduction in the vitamin E levels and renal function compared to the Fe group alone. We concluded that NO plays an important role in protecting the kidney from iron-induced nephrotoxicity. NO synthase blockade enhances iron-mediated renal toxicity in this model.

scholarly journals Mouse Models of Nitric Oxide Synthase Deficiency

2000 ◽  
Vol 11 (suppl 2) ◽  
pp. S120-S123
Author(s):  
PAUL L. HUANG
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Knockout Mice ◽  
Vascular Tone ◽  
Tissue Injury ◽  
No Synthase ◽  
Oxide Synthase ◽  
Pathologic Processes ◽  
Diastolic Cardiac Function ◽  
Inducible Nos

Abstract. Knockout mice for each of the three nitric oxide (NO) synthase (NOS) genes have been generated. Their phenotypes reflect the roles of each NOS isoform in physiologic and pathologic processes. This article reviews how neuronal NOS (nNOS) and endothelial NOS (eNOS) knockout mice have contributed to our knowledge of the roles of NO in cerebral ischemia, cardiovascular processes, and the autonomic nervous system. In some instances, the effects of NO produced by one isoform antagonize the effects of NO produced by another isoform. For example, after cerebral ischemia, the nNOS isoform is involved in tissue injury, whereas the eNOS isoform is important in maintaining blood flow. All three isoforms are expressed in the respiratory tract, but only the nNOS isoform appears to be involved in modulating airway responsiveness and only the inducible NOS isoform appears to respond to antigen stimulation. In the cardiovascular system, endothelial NO is important for vascular tone, systolic and diastolic cardiac function, vascular proliferative responses to injury, platelet aggregation, and hemostasis.

scholarly journals Role of Nitric Oxide in the Cardiovascular and Renal Systems

2018 ◽  
Vol 19 (9) ◽  
pp. 2605 ◽  
Author(s):  
Ashfaq Ahmad ◽  
Sara Dempsey ◽  
Zdravka Daneva ◽  
Maleeha Azam ◽  
Ningjun Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Beneficial Effects ◽  
Disease States ◽  
Potent Vasodilator ◽  
Gaseous Transmitters ◽  
Experimental Approaches ◽  
Specific Receptors

The gasotransmitters are a family of gaseous signaling molecules which are produced endogenously and act at specific receptors to play imperative roles in physiologic and pathophysiologic processes. As a well-known gasotransmitter along with hydrogen sulfide and carbon monoxide, nitric oxide (NO) has earned repute as a potent vasodilator also known as endothelium-derived vasorelaxant factor (EDRF). NO has been studied in greater detail, from its synthesis and mechanism of action to its physiologic, pathologic, and pharmacologic roles in different disease states. Different animal models have been applied to investigate the beneficial effects of NO as an antihypertensive, renoprotective, and antihypertrophic agent. NO and its interaction with different systems like the renin–angiotensin system, sympathetic nervous system, and other gaseous transmitters like hydrogen sulfide are also well studied. However, links that appear to exist between the endocannabinoid (EC) and NO systems remain to be fully explored. Experimental approaches using modulators of its synthesis including substrate, donors, and inhibitors of the synthesis of NO will be useful for establishing the relationship between the NO and EC systems in the cardiovascular and renal systems. Being a potent vasodilator, NO may be unique among therapeutic options for management of hypertension and resulting renal disease and left ventricular hypertrophy. Inclusion of NO modulators in clinical practice may be useful not only as curatives for particular diseases but also for arresting disease prognoses through its interactions with other systems.

scholarly journals Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte

1993 ◽  
Vol 90 (23) ◽  
pp. 11419-11423 ◽  
Author(s):  
I G Charles ◽  
R M Palmer ◽  
M S Hickery ◽  
M T Bayliss ◽  
A P Chubb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cdna Clone ◽  
Articular Chondrocytes ◽  
Interleukin 1 ◽  
Cell Types ◽  
No Synthase ◽  
Human Chondrocyte ◽  
Oxide Synthase ◽  
Different Cell Types ◽  
Inducible Nitric Oxide

Incubation of human articular chondrocytes with interleukin 1 beta results in the time-dependent expression of nitric oxide (NO) synthase. We report here the isolation of a cDNA clone which encodes a protein of 1153 amino acids with a molecular mass of 131,213 Da and a calculated isoelectric point of 7.9. CHO cells transfected with a plasmid harboring this cDNA clone expressed NO synthase activity that was inhibited by some L-arginine analogues. The deduced amino acid sequence of the human chondrocyte inducible NO synthase shows 51% identity and 68% similarity with the endothelial NO synthase and 54% identity and 70% similarity with the neuronal NO synthase. The similarity (88%) between the human chondrocyte NO synthase cDNA sequence and that reported for the murine macrophage suggests that the inducible class of enzyme is conserved between different cell types and across species.

Effects of ATP and bradykinin on endothelial cell Ca2+ homeostasis and formation of cGMP and prostacyclin

1993 ◽  
Vol 265 (6) ◽  
pp. C1620-C1629 ◽  
Author(s):  
E. C. Gosink ◽  
E. J. Forsberg
Keyword(s):  
Nitric Oxide ◽  
Early Time ◽  
Receptor Occupancy ◽  
Cell Types ◽  
No Synthase ◽  
Time Points ◽  
No Formation ◽  
Per Se ◽  
Cgmp Formation

ATP and bradykinin are known to activate Ca2+ release from intracellular Ca2+ pools as well as induce the influx of Ca2+ in many cell types. In adrenal medulla endothelial cells, we found that ATP and bradykinin could activate Ca2+ influx, although Ca2+ influx did not appear to be due to depletion of intracellular Ca2+ pools per se, since depletion of intracellular Ca2+ pools with thapsigargin reduced rather than enhanced both unidirectional and steady-state 45Ca2+ uptake. In addition, Ca2+ influx, activated by ATP but not bradykinin, was mostly abolished after agonist removal in cells in which intracellular Ca2+ pools had not been allowed to refill, suggesting that continued receptor occupancy was necessary for ATP to activate Ca2+ influx. The role of Ca2+ in activating guanosine 3',5'-cyclic monophosphate (cGMP) formation [a marker for nitric oxide (NO) secretion] and prostacyclin (PGI2) secretion was also studied. Bradykinin-induced cGMP and PGI2 formation and ATP-induced PGI2 formation each required Ca2+ release from intracellular Ca2+ pools, since depletion of these pools with thapsigargin inhibited their formation. In contrast, ATP-induced cGMP formation, particularly at early time points, did not appear to require either Ca2+ release or Ca2+ influx. This suggests that ATP, but not bradykinin, either induces Ca(2+)-independent NO formation or that ATP stimulates the generation of cGMP independently of NO. The latter supposition is supported by our observation that NO synthase inhibitors inhibited ATP-induced cGMP formation by at most 50%.

scholarly journals INTRACELLULAR TARGETS OF PROAPOPTOTIC INFLUENCE OF GASEOUS TRANSMITTERS

2012 ◽  
Vol 67 (10) ◽  
pp. 77-81 ◽  
Author(s):  
L. A. Tashireva ◽  
E. G. Starikova ◽  
V. V. Novitskii ◽  
N. V. Ryazantseva
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Transmembrane Potential ◽  
Molecular Targets ◽  
Jurkat Cells ◽  
Mitochondrial Transmembrane Potential ◽  
Caspase 9 ◽  
Gaseous Transmitters ◽  
Intracellular Targets

Main molecular targets of nitric oxide, hydrogen sulfide and carbon monoxide proapoptotic action in Jurkat cells were determined in this study. Decrease of mitochondrial transmembrane potential was shown during all three gases action. Reason of this event is the Bcl-2 family members disbalance. Proapoptotic proteins release after mitochondrion membranes permeabilisation could be abolished by protein xIAP inhibition of caspase -9 and-3 activity during NO and CO application. 

scholarly journals Lipopolysaccharide induces relaxation in lung pericytes by an iNOS-independent mechanism

2000 ◽  
Vol 278 (5) ◽  
pp. L880-L887 ◽  
Author(s):  
Cecilia L. Speyer ◽  
Christopher P. Steffes ◽  
James G. Tyburski ◽  
Jeffrey L. Ram
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Cell Types ◽  
Inhibitory Effect ◽  
No Synthase ◽  
No Production ◽  
No Donor ◽  
Independent Mechanism ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Lipopolysaccharide (LPS)-regulated contractility in pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during inflammation and sepsis. LPS has been shown to regulate inducible nitric oxide (NO) synthase (iNOS) in various cell types, leading to NO generation, which is associated with vasodilatation. The purpose of this study was to test the hypothesis that LPS can regulate relaxation in lung pericytes and to determine whether this relaxation is mediated through the iNOS pathway. As predicted, LPS stimulated NO synthesis and reduced basal tension by 49% ( P < 0.001). However, the NO synthase inhibitors N ω-nitro-l-arginine methyl ester, aminoguanidine, and N ω-monomethyl-l-arginine did not block the relaxation produced by LPS. In fact, aminoguanidine and N ω-monomethyl-l-arginine potentiated the LPS response. The possibility that NO might mediate either contraction or relaxation of the pericyte was further investigated through the use of NO donor compounds; however, neither sodium nitroprusside nor S-nitroso- N-acetylpenicillamine had any significant effect on pericyte contraction. The inhibitory effect of aminoguanidine on LPS-stimulated NO production was confirmed. This ability of LPS to inhibit contractility independent of iNOS was also demonstrated in lung pericytes derived from iNOS-deficient mice. This suggests the presence of an iNOS-independent but as yet undetermined pathway by which lung pericyte contractility is regulated.

Abstract 493: Renal Injury Induced by Nitric Oxide Depletion is Prevented by Concomitant Inhibition of Hydrogen Sulfide and/or Carbon Monoxide Production

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sebastiaan Wesseling ◽  
Joost O Fledderus ◽  
Marianne C Verhaar ◽  
Jaap A Joles
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Carbon Monoxide ◽  
Renal Function ◽  
Hydrogen Sulfide ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
No Synthase ◽  
Heme Oxygenase 1 ◽  
Plasma Urea

Chronic nitric oxide (NO) depletion induces hypertension and renal damage. Hydrogen sulfide (H 2 S) producing cystathionine-γ-lyase (CSE) and carbon monoxide (CO) producing heme oxygenase-1 (HO-1) appear to be protective in mechanically-induced renal injury (e.g. ischemia reperfusion). However, inhibition of CSE can reduce drug-induced renal injury (e.g. cisplatin). The role of renal H 2 S and HO-1 during chronic NO depletion is unknown. We hypothesized that renal injury secondary to NO depletion via inhibition of NO synthase is diminished by additional H 2 S depletion via inhibition of CSE. Rats (n=6/group) were treated with inhibitors of NO synthase (L-nitroarginine; LNNA), CSE (DL-propargylglycine; PAG), or HO-1 (Sn(IV) protoporphyrin IX dichloride; SnPP) for 1 or 4 weeks or with combinations (LNNA+PAG; LNNA+SnPP; PAG+SnPP or LNNA+PAG+SnPP) for 4 weeks. One week LNNA reduced urinary NOx excretion (35±2% vs baseline) and induced hypertension (173±12 vs. 137±3 mmHg; P<0.01) but renal function remained normal. Four weeks of LNNA further reduced NOx (7±1%), worsened hypertension (223±10 mmHg) and caused renal injury; plasma urea (17±4 vs 7±1 mmol/L; P<0.05), proteinuria (144±35 vs 17±2 mg/d; P<0.01). PAG or SnPP had no effect. NOx was reduced by PAG and increased by SnPP. Renal H 2 S production was completely blocked by PAG and enhanced by SnPP at 1 and 4 weeks. Renal HO-1 expression was induced by LNNA at 4 weeks and by PAG and SnPP at 1 and 4 weeks (all P<0.001). Adding PAG, SnPP, or both, to LNNA did not affect hypertension but preserved renal function. Combining PAG and SnPP had no effect on blood pressure or renal function. Reduction of urine NOx by LNNA was not affected by additional PAG (8±2%) but was ameliorated by adding SnPP (37±4%) or PAG+SnPP (42±9%). Renal H 2 S production was completely inhibited with all PAG-combinations (P<0.01), but was twofold enhanced by LNNA+SnPP (P<0.01). Renal HO-1 expression was increased by all combinations. NO depletion resulted in hypertension and progressive renal injury that was prevented by concomitant inhibition of CSE and/or HO-1. Depletion of H 2 S and CO in the absence of NO depletion had no effect on blood pressure and renal function. These data suggest that pathways from NO depletion to renal injury run via H 2 S or CO.

Nitric oxide and reactive oxygen species in vascular injury

1995 ◽  
Vol 61 ◽  
pp. 33-45 ◽  
Author(s):  
Homero Rubbo ◽  
Margaret Tarpey ◽  
Bruce A. Freeman
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Tissue Injury ◽  
Cell Types ◽  
Protective Role ◽  
High Rate ◽  
No Production ◽  
Radical Species ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

Nitric oxide (.NO), a free radical species produced by several mammalian cell types, plays a role in regulation of vascular, neurological and immunological signal transduction and function. The role of .NO in cytotoxic events is acquiring increased significance. The high rate of production and broad distribution of sites of production of .NO, combined with its facile direct and indirect reactions with metalloproteins, thiols and various oxygen radical species, assures that .NO will play a central role in regulating vascular, physiological and cellular homoeostasis, as well as critical intravascular free radical and oxidant reactions. At the same time, there are contradictions as to whether .NO mediates or limits free-radical-mediated tissue injury, and uncertainty regarding its mechanisms of action. .NO has been portrayed as a pathogenic mediator during ischaemia-reperfusion, and inflammatory and septic tissue injury. In contrast, cell-, metal- and oxidant-induced lipoprotein oxidation events, as well as hepatic, cerebrovascular, pulmonary and myocardial inflammatory and ischaemia-reperfusion injury studies, show convincingly that stimulation of endogenous .NO production or exogenous administration of .NO-donating molecules can serve a protective role by inhibition of often oxidant-related mechanisms. The final outcome of toxic versus tissue-protective reactions of .NO will depend on several factors, including sites and relative concentrations of individual reactive species and their diffusion distances. The following sections address these issues and conclude with a proposal as to how .NO serves as a central regulator of oxidant reactions and diverse free radical-related disease processes.

scholarly journals An Update on Hydrogen Sulfide and Nitric Oxide Interactions in the Cardiovascular System

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Dan Wu ◽  
Qingxun Hu ◽  
Deqiu Zhu
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Cardiovascular System ◽  
Posttranslational Modification ◽  
Chemical Interaction ◽  
Protein Activity ◽  
Wide Range ◽  
Gaseous Transmitters ◽  
Heart Injury ◽  
Regulatory Functions

Hydrogen sulfide (H2S) and nitric oxide (NO) are now recognized as important regulators in the cardiovascular system, although they were historically considered as toxic gases. As gaseous transmitters, H2S and NO share a wide range of physical properties and physiological functions: they penetrate into the membrane freely; they are endogenously produced by special enzymes, they stimulate endothelial cell angiogenesis, they regulate vascular tone, they protect against heart injury, and they regulate target protein activity via posttranslational modification. Growing evidence has determined that these two gases are not independent regulators but have substantial overlapping pathophysiological functions and signaling transduction pathways. H2S and NO not only affect each other’s biosynthesis but also produce novel species through chemical interaction. They play a regulatory role in the cardiovascular system involving similar signaling mechanisms or molecular targets. However, the natural precise mechanism of the interactions between H2S and NO remains unclear. In this review, we discuss the current understanding of individual and interactive regulatory functions of H2S and NO in biosynthesis, angiogenesis, vascular one, cardioprotection, and posttranslational modification, indicating the importance of their cross-talk in the cardiovascular system.

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